Search for allosteric disulfide bonds in NMR structures

Schmidt, Bryan; Hogg, Philip J.

doi:10.1186/1472-6807-7-49

Cited by 77 publications

(94 citation statements)

References 30 publications

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“…The general trends observed in this sample were quite consistent with the results obtained by other authors (Schmidt et al, 2006;Schmidt and Hogg, 2007) for three different protein sets.…”

Section: Discussionsupporting

confidence: 92%

“…The minimum (2.5 kJ mol Ͳ1 ) and the maximum (84.5 kJ mol Ͳ1 ) values of DSE correspond to the torsion angles combinations (60º, 60º, ±83º, 60º, 60º) and (0º, 0º, 0º, 0º, 0º), respectively (Schmidt et al, 2006). Despite its simplicity, this equation has been successfully applied for a semiͲquantitative evaluation of the strain energy in disulfide bonds (Schmidt et al, 2006;Schmidt and Hogg, 2007).…”

Section: Methodsmentioning

confidence: 99%

“…These structural elements have a significant role in the thermal stability and function of proteins (Bhattacharyya et al, 2004;Creighton, 1988;Hogg, 2003;Klink et al, 2000;Sardiu et al, 2007). From an evolutionary perspective, these bonds are a relatively recent addition to protein structure Jordan et al, 2005;Schmidt and Hogg, 2007) According to the respective functions, the disulfide bonds can then be classified as structural, catalytic or allosteric (Schmidt et al, 2006;Schmidt and Hogg, 2007). Schmidt et al (2006) have performed a thorough analysis of disulfides present in the XͲray structures of the PDB database, and found that both catalytic and allosteric disulfides fell into particular structural categories.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Conformational characterization of disulfide bonds: A tool for protein classification

Marques¹,

Fonseca²,

Drury³

et al. 2010

Journal of Theoretical Biology

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“…The general trends observed in this sample were quite consistent with the results obtained by other authors (Schmidt et al, 2006;Schmidt and Hogg, 2007) for three different protein sets.…”

Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Conformational characterization of disulfide bonds: A tool for protein classification

Marques¹,

Fonseca²,

Drury³

et al. 2010

Journal of Theoretical Biology

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“…27,30 The distance between the ␣-carbons of the Cys3-Cys5 bond is 4.01 Å (Table 2, average of the 2 structures), compared with a mean of 5.62 Å for all disulfides in a nonredundant set of X-ray structures. 31 The crossveinless 2 and procollagen 2A C domain structures were used to predict the structure of the VWF C2 domain using the I-TASSER protein structure prediction tool. 19 It is apparent that the structures have a similar architecture and the pairing of the cysteine residues is the same (Figure 3C).…”

Section: Predicted Structure Of the C2 Domain Of Vwfmentioning

confidence: 99%

Lateral self-association of VWF involves the Cys2431-Cys2453 disulfide/dithiol in the C2 domain

Ganderton

Wong

Schroeder

et al. 2011

Blood

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VWF is a plasma protein that binds platelets to an injured vascular wall during thrombosis. When exposed to the shear forces found in flowing blood, VWF molecules undergo lateral self-association that results in a meshwork of VWF fibers. Fiber formation has been shown to involve thiol/disulfide exchange between VWF molecules. A C-terminal fragment of VWF was expressed in mammalian cells and examined for unpaired cysteine thiols using tandem mass spectrometry (MS). The VWF C2 domain Cys2431-Cys2453 disulfide bond was shown to be reduced in approximately 75% of the molecules. Fragments containing all 3 C domains or just the C2 domain formed monomers, dimers, and higher-order oligomers when expressed in mammalian cells. Mutagenesis studies showed that both the Cys2431-Cys2453 and nearby Cys2451-Cys2468 disulfide bonds were involved in oligomer formation. Our present findings imply that lateral VWF dimers form when a Cys2431 thiolate anion attacks the Cys2431 sulfur atom of the Cys2431-Cys2453 disulfide bond of another VWF molecule, whereas the Cys2451-Cys2468 disulfide/dithiol mediates formation of trimers and higher-order oligomers. These observations provide the basis for exploring defects in lateral VWF association in patients with unexplained hemorrhage or thrombosis. (Blood. 2011;118(19): 5312-5318) IntroductionVWF is a large, multimeric glycoprotein responsible for chaperoning the blood coagulation cofactor factor VIII and tethering platelets to the site of vascular endothelial injury. 1 It is synthesized by vascular endothelial cells and megakaryocytes and circulates as a series of multimers containing variable numbers of 500-kDa dimeric units. Circulating multimers range between 500 and 20 000 kDa in size, and although any size multimer is able to chaperone factor VIII, 2 it is the only the largest sizes that are able to effectively tether platelets. Each subunit contains binding sites for collagen and for platelet glycoproteins Ib and ␣IIb␤3. 1 Multimer size is regulated in the circulation. An excess of high-molecular-weight multimers can cause unwanted thrombosis and is associated with thrombotic thrombocytopenic purpura, 3 whereas a paucity of large multimers is associated with the bleeding disorder VWD. 1 Under normal conditions, the size of VWF multimers is controlled by ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 motifs) proteolysis of the Tyr1605-Met1606 peptide bond in the A2 domain. 4 The tertiary and quaternary structure of VWF is influenced by the shear forces typically found in flowing blood. VWF undergoes a shear-dependent conformational change, 5 and individual molecules can self-associate under both static 6 and shear conditions. 7-9 VWF reversibly transitions from a loosely coiled ball to an elongated structure in response to shear. 5,10,11 Self-association of VWF has been reported in different systems. Soluble VWF perfused over a VWF-coated surface undergoes "homotypic" self-association that facilitates platelet adhesion. 9 In addition, VWF self-associates into ...

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“…The dihedral strain energy (DSE) was determined as described previously (25,26). Briefly, the DSE of each intramolecular disulfide bond was predicted from the magnitudes of the five dihedral torsion angles () that define the disulfide using the following empirical formula (25,26):…”

Section: Cells and Transfections Spodoptera Frugiperda (Sf9) Cells Amentioning

confidence: 99%

Baculovirus GP64 Disulfide Bonds: the Intermolecular Disulfide Bond of Autographa californica Multicapsid Nucleopolyhedrovirus GP64 Is Not Essential for Membrane Fusion and Virion Budding

Blissard

2010

J Virol

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The GP64 envelope glycoprotein of the Autographa californica nucleopolyhedrovirus (AcMNPV) is a class III viral membrane fusion protein that is triggered by low pH during entry. Unlike most other viral fusion protein trimers, the monomers of GP64 are covalently linked to each other within the trimer by a single intermolecular disulfide bond (Cys24OCys372). Single or paired alanine substitutions for Cys24 and Cys372 resulted in lower-efficiency transport of GP64 to the cell surface. Surprisingly, these mutated GP64s induced syncytium formation, and normalized fusion activities were approximately 30% of that from wild-type (WT) GP64. Heat treatment (37°C) did not further reduce fusion activity of GP64 constructs with a disrupted intermolecular disulfide bond, suggesting that the GP64 trimers were relatively thermostable in the absence of the intermolecular disulfide bond. In addition, analysis of binding by a conformation-specific monoclonal antibody (MAb) suggested that the low-pH-induced refolding of those GP64 constructs was generally similar to that of WT GP64. In addition to its critical role in membrane fusion, GP64 is also necessary for efficient budding. When GP64 constructs containing a disrupted intermolecular disulfide bond (Cys24OCys372) were displayed at the cell surface at levels comparable to those of WT GP64, virion budding efficiency ranged from approximately 39 to 88%, indicating that the intermolecular disulfide bond is not required for virion budding. However, GP64 proteins with a disrupted intermolecular disulfide could not rescue a GP64-null bacmid. We also examined the 6 conserved intramolecular disulfide bonds using single and paired alanine substitution mutations. None of the GP64 constructs with disrupted intramolecular disulfide bonds were capable of mediating pH-triggered membrane fusion, indicating that the intramolecular disulfide bonds are all necessary for membrane fusion. Thus, while the intramolecular disulfide bonds of GP64 appear to serve critical roles in membrane fusion, the unusual intermolecular disulfide bond was not critical for membrane fusion or virion budding yet appears to play an unknown role in viral infectivity.

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Search for allosteric disulfide bonds in NMR structures

Abstract: Background: Allosteric disulfide bonds regulate protein function when they break and/or form. They typically have a -RHStaple configuration, which is defined by the sign of the five chi angles that make up the disulfide bond.

Cited by 77 publications

References 30 publications

Conformational characterization of disulfide bonds: A tool for protein classification

Conformational characterization of disulfide bonds: A tool for protein classification

Lateral self-association of VWF involves the Cys2431-Cys2453 disulfide/dithiol in the C2 domain

Baculovirus GP64 Disulfide Bonds: the Intermolecular Disulfide Bond of Autographa californica Multicapsid Nucleopolyhedrovirus GP64 Is Not Essential for Membrane Fusion and Virion Budding

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